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At least 451 records · Page 25Linked to original sources
PubMed2006

Kinetic model of drug distribution in the urinary bladder wall following intravesical instillation.

Intravesical administration of cytotoxic agents is commonly used in urological practice for treatment of superficial bladder cancer. The leading motive is optimisation of drug delivery near the site of action and reduction of systemic toxicity. Bladder pharmacokinetics is complicated by several mechanisms. The objectives of this work were to develop a kinetic model of drug distribution in the bladder wall following intravesical instillation and to study the effect of various parameters on tissue and systemic drug exposure and explore the potential benefits of permeability enhancing effects of chitosan (CH) and polycarbophil (PC) through simulation. Key elements of the model are variable urinary drug concentration due to urine formation and voiding, biphasic diffusion in the bladder tissue and systemic absorption. Model parameters were estimated from bladder-tissue concentration profiles obtained in previous in vitro experiments with pipemidic acid (PPA) as a model drug. The results support further investigations on application of CH and PC in intravesical drug delivery. Both polymers increase permeability of the bladder wall by diffusion enhancement in the urothelium and presumably by improving the contact with the bladder surface. The developed mathematical model could serve for optimisation of intravesical drug delivery and future development of intravesical drug delivery systems.

Acrylic Resins↗
PubMed1991

A kinetic model for the alpha-thrombin-catalyzed conversion of plasma levels of fibrinogen to fibrin in the presence of antithrombin III.

In this study we report a kinetic model for the alpha-thrombin-catalyzed production of fibrin I and fibrin II at pH 7.4, 37 degrees C, gamma/2 0.17. The fibrin is produced by the action of human alpha-thrombin on plasma levels of human fibrinogen in the presence of the major inhibitor of alpha-thrombin in plasma, antithrombin III (AT). This model quantitatively accounts for the time dependence of alpha-thrombin-catalyzed release of fibrinopeptides A and B concurrent with the inactivation of alpha-thrombin by AT and delineates the concerted interactions of alpha-thrombin, fibrin(ogen), and AT during the production of a fibrin clot. The model also provides a method for estimating the concentration of alpha-thrombin required to produce a clot of known composition and predicts a direct relationship between the plasma concentration of fibrinogen and the amount of fibrin produced by a bolus of alpha-thrombin. The predicted relationship between the concentration of fibrinogen and the amount of fibrin produced in plasma provides a plausible explanation for the observed linkage between plasma concentrations of fibrinogen and the risk for ischemic heart disease.

Antithrombin III↗
PubMedDate not supplied

[Kinetic model of primary processes of photosynthesis in chloroplasts. Fast phase of chlorophyll fluorescence induction under light of various intensity].

A kinetic model was developed, which describing the system of generation and consumption of the transmembrane electrochemical proton potential delta mu H+ in primary photosynthetic processes. The model describes the catalytic cycles of photosystems I and II and the cytochrome b/f complex, as well as the ATP synthesis and passive leakage of H+, K+ [symbol: see text] Cl- ions through the thylakoid membrane. The dependence of the electron transfer rates on the value of transmembrane electric potential was taken into account. The model was applied to describe the experimental data on the registration of the fast phase of fluorescence induction. The model gives a realistic description of the fast phase of induction curves at different light intensities (from high to low).

Adenosine Triphosphate↗
PubMed1992

Sensitivity increase in the photophobic response of Halobacterium halobium reconstituted with retinal analogs: a novel interpretation for the fluence-response relationship and a kinetic modeling.

Phoborhodopsin (also called sensory rhodopsin II) is a photoreceptor protein which mediates photophobic responses of Halobacterium halobium to blue-green light. Under conditions where the synthesis of the chromophore retinal is inhibited, the photophobic system is reconstituted in vivo by incorporation of all-trans retinal or retinal analogs into the apoprotein of phoborhodopsin. Retinal analogs which retard the cyclic photoreaction kinetics of phoborhodopsin increase significantly the sensitivity of the photophobic response. This supports the previously reported hypothesis that signal amplification occurs during the lifetime of intermediate states of the photocycle. The sensitivity increase caused by the chromophore substitution is observed in cells at several different growth stages, i.e. the naturally occurring chromophore (all-trans retinal) does not produce maximal sensitivity at any stage of the culture growth. These results are difficult to interpret in terms of the proposal by Marwan et al. (J. Mol. Biol. 199, 663-664, 1988) that only a single photon is sufficient to cause the photobehavioral response in cells containing native phoborhodopsin. A new interpretation for the fluence-response curves is described based in part on their Poisson statistical analysis. Further, a kinetic model which relates the receptor photochemical reaction cycle to the behavioral response is developed, which accounts for both the sensitivity increase and the shape of the fluence-response curves.

Archaeal Proteins↗
PubMed1987

Kinetic modeling of hormone release: application to time-averaged met-enkephalin release.

The time course of hormone concentrations in response to a stimulus can be characterized with kinetic methods to express rates of hormone release and elimination, total amount of hormone release and expected best times for blood sampling. Routine application of kinetic methods should increase the sensitivity and applicability of hormonal challenge tests. Applications to the TRH test and to prolactin release measurements are reviewed. A new kinetic model for continuously collected samples is applied to measurements of met-enkephalin release in rats. Calculations indicated an initial concentration of 1876 pg/ml and a ventricular volume of distribution of 0.25 ml. After exposure of rats to nitrous oxide, the rate of release of met-enkephalin-like activity into the ventricles rose from 3.4 to 8.3 pg/min.

Animals↗
PubMed1990

Kinetic model for membrane transport. 2. Time lag and overshoot.

A lag time during the period of variation in solute concentration in the receiver phase and overshoot in that in the membrane phase have been predicted to occur with a kinetic model for membrane transport which takes into account both the membrane volume and the partitioning kinetics (Makino et al., Biophys. Chem. 35 (1990) 85). The duration of the lag time becomes longest when the donor and receiver phases have the same volume. This maximum grows in length with increase in the partition coefficient, tending to be proportional to the volume fraction of the receiver phase. Moreover, it displays an increase in length with decreasing membrane volume fraction. Overshoot occurs only when the volume fraction of the receiver phase is greater than that of the donor. Overshoot is observed during the earlier stages of membrane transport when the partition coefficient is smaller or the volume fraction of the receiver phase is larger.

Biological Transport↗
PubMed2000

Kinetic model for 5-fluorouridine degradation. Catalytic effect of 5-fluorouracil.

The effects of 5-fluorouridine (5-FUR, CAS 316-46-1) degradation products, 5-fluorouracil (5-FU, CAS 51-21-8) and D-ribose (CAS 50-69-1), on its degradation rate was investigated following a 2(3) factorial design. The experimental data fitted to the proposed mathematical model which includes two parallel degradation mechanisms: the first one, a second order bimolecular reaction involving both 5-FUR and 5-FU, and the second, a first order one. Experimental data obtained show a high variability. Both graphic and statistical analysis of the experiments for which a full kinetic model was applied manifested that the degradation mechanism included an autocatalytic route and confirmed the role of the 5-FU on the hydrolysis of 5-FUR.

Algorithms↗
PubMed2001

Kinetic modeling of liquid-phase adsorption of reactive dyes and metal ions on chitosan.

The rates of adsorption of three commercial reactive dyes and Cu(II) from water in the absence and presence of complexing agents using chitosan were measured at 30 degrees C. Three simplified kinetic models, i.e., pseudo-first-order, pseudo-second-order, and intraparticle diffusion, were tested to investigate the adsorption mechanisms. It was shown that the adsorption of reactive dyes and Cu(II) in the absence of complexing agents could be best described by the intraparticle diffusion model, whereas that of Cu(II) in the absence of complexing agents such as EDTA, citric acid, and tartaric acid by the pseudo-second-order equation. Kinetic parameters of the three models and the normalized standard deviations between the measured and predicted results were also calculated and discussed.

Adsorption↗
PubMed2005

Kinetic modeling of the adsorption of basic dyes by kudzu.

The use of kudzu, a rapidly growing, high-climbing perennial leguminous vine, for the adsorption of basic dyes from aqueous solution has been investigated at various initial dye concentrations, masses of kudzu, and agitation rates. The extent and rate of adsorption of the three basic dyes (Basic Red 22, Basic Yellow 21, and Basic Blue 3) were analyzed using a pseudo-first-order and a pseudo-second-order kinetic model. While both rate mechanisms provided an acceptable degree of correlation with the experimental sorption rate data, the pseudo-second-order model gave a much higher degree of correlation, suggesting that this model could be used in design and simulation applications.

Adsorption↗
PubMed1986

Kinetic model of glucose-6-phosphate dehydrogenase from red blood cells. Parameter estimation from progress curves and simulation of regulatory properties.

A kinetic model of human and mouse glucose-6-phosphate dehydrogenase is presented which takes into account the substrates and all inhibitors of significant importance in the red cell. The parameter values were estimated by analysis of progress curves. The applicability of a new method based on non-linear regression to complex enzyme kinetics was proved. The in vivo-regulation of glucose-6-phosphate dehydrogenase is examined by determining elasticity coefficients and by using simple simulation experiments. The model is convenient to describe the behaviour of enzyme activity under physiological conditions.

Adenosine Triphosphate↗
PubMedDate not supplied

Improvement of decisions regarding hemodialysis patients by urea kinetic modeling.

The potentials for improving decisions about adequacy of dialysis (AD) and daily protein intake (DPI) by urea kinetic modeling (UKM) were examined. Four nephrologists evaluated AD, DPI, and metabolic stability in 62 patients. UKM was done three times; but the results were not revealed. Clinicians' decisions were then compared with UKM measures of effective dialysis (Kt/V) and protein catabolic rate (pcr). Detection of inadequately treated patients by the clinicians was poor (28%, Kt/V less than 1.0; and 40%, Kt/V less than 0.9). Specificities of the clinicians' decisions were 0.96 and 0.92, respectively. Combining pcr and consensus decisions, 59 patients could be assigned a probable DPI. Using this as "gold standard," the average clinician detected 77% of 13 low DPIs. Single or triple pcr determinations alone detected 77% or 62%, respectively. Specificities were 0.91, 0.85, and 1.0. Simulated decision making suggested that combining pcr with clinical evaluation in a logical way would lead to detection of most patients with low DPI. Qualitative data from individual patient cases causing controversies are presented and discussed. It is concluded the UKM should be used routinely to assess the adequacy of dialysis and daily protein intake.

Adult↗
PubMed1993

A kinetic model of the circulatory regulation of tissue plasminogen activator during exercise, epinephrine infusion, and endurance training.

A computer simulation of the circulatory system was used to kinetically model secretion, inhibition, and clearance of tissue plasminogen activator (t-PA) during three different processes that increase active t-PA levels: epinephrine infusion, exercise, and endurance training. Infusion of epinephrine stimulated an increase in t-PA secretion that was proportional to the plasma epinephrine concentration. In addition, epinephrine infusion increased hepatic blood flow and t-PA clearance, thus slowing the increase of plasma t-PA levels. During exercise, t-PA levels increased due both to increased t-PA secretion and to decreased clearance secondary to reduced hepatic blood flow. The increase in t-PA secretion during exercise was directly proportional to the epinephrine concentration in blood with the same ratio of t-PA secretion to epinephrine as found during epinephrine infusion, suggesting that increased plasma epinephrine during exercise was the primary stimulus for t-PA secretion. Lastly, the simulation predicted that 6 months of endurance training produced a decrease in resting plasminogen activator inhibitor type 1 (PAI-1) secretion, resulting in less t-PA inhibition and an overall increase in active t-PA after training. Accurate analysis of the regulation of active t-PA levels in blood required simultaneous modeling of t-PA and PAI-1 secretion, hepatic clearance, and inhibition of t-PA by PAI-1.

Computer Simulation↗
PubMed2002

A kinetic model of N-nitrosodimethylamine (NDMA) formation during water chlorination/chloramination.

Experiments were conducted to investigate the hypothesis that N-nitrosodimethylamine (NDMA) is a potential disinfection by-product. NDMA was formed by the reaction of dimethylamine (DMA) with monochloramine and also with free chlorine in the presence of ammonia. We proposed a mechanism for NDMA formation which does not require the presence of nitrite as in N-nitrosation. The critical NDMA formation reactions consist of i) the formation of monochloramine by combination of free chlorine with ammonia, ii) the formation of 1,1-dimethylhydrazine (UDMH) intermediate from the reaction of DMA with monochloramine followed by, iii) the oxidation of UDMH by monochloramine to NDMA, and iv) the reversible chlorine transfer reaction between free chlorine/monochloramine and DMA which is parallel with i) and ii). A kinetic model was developed to validate the proposed mechanism.

Carcinogens↗
PubMed2006

Predicted serum folate concentrations based on in vitro studies and kinetic modeling are consistent with measured folate concentrations in humans.

The nutritional quality of new functional or fortified food products depends on the bioavailability of the nutrient(s) in the human body. Bioavailability is often determined in human intervention studies by measurements of plasma or serum profiles over a certain time period. These studies are time and cost consuming and often appear to lack an optimal study design, leading to follow-up intervention trials. Therefore, an alternative approach is needed that will optimize the development of new products. This study describes an approach to predict human serum concentrations after the consumption of (fortified) food products. The concept is based on the integration of in vitro results with kinetic modeling. As a case study, human serum folate concentrations were predicted after the consumption of folate-fortified milk products for 4 wk. Oral bioavailability was investigated using a step-wise approach in which luminal bioaccessibility and intestinal absorption were independently evaluated. Subsequently, these in vitro data were integrated in a kinetic mathematical (in silico) model to predict serum folate concentrations after the intake of a single dose and during long-term consumption. This approach was evaluated in comparison to a human intervention study in which folic acid-fortified milk products were tested for their effect on serum folate concentrations. A high predictive quality of this alternative in vitro/in silico approach was demonstrated. Finally, this methodology was applied to predict serum folate concentrations after intake of different fortified milk products for 4 wk, showing its benefits for the development of new nutritional products.

Dairy Products↗
PubMed2005

Kinetic modeling of plasma leucine levels during continuous venovenous extracorporeal removal therapy in neonates with maple syrup urine disease.

A kinetic modeling of leucine plasma concentration changes is proposed to describe the plasma leucine reduction rate during continuous extracorporeal removal therapy (CECRT) in neonates with maple syrup urine disease. Data were obtained from seven neonates using a bicompartmental model for the best fitted curve of plasma leucine decrease during CECRT. During the first 3 h, leucine plasma levels decreased according to an exponential curve: [Leu](t) = [Leu](i) x 0.95 x 10(-0.09t) where [Leu](t) is the leucine plasma level (mumol/L) at time t (h) during CECRT and [Leu](I) is the initial plasma level. From h 4 to the end of CECRT, a second exponential curve was observed: [Leu](t) = [Leu](i) x 0.74 x 10(-0.05t). Plasma leucine levels obtained from three other neonates were similar to those predicted by the model. The apparent distribution volumes for leucine that correspond to the two exponential equations obtained were calculated from the leucine mass removal collected in the spent dialysate and ultrafiltrate. The distribution volume was 34 +/- 3% of body weight during the first 3 h of CECRT and 72 +/- 7% from h 4 to the end of CECRT. These figures are similar to known values for the extracellular water compartment and for total body water in the newborn. The findings suggest that leucine handling during CECRT is similar to that of nonprotein-bound small-molecular-weight solutes such as urea.

Body Water↗
PubMed2005

Using a kinetic model that considers cell segregation to optimize hEGF expression in fed-batch cultures of recombinant Escherichia coli.

Growth inhibition of recombinant Escherichia coli during the expression of human epidermal growth factor was observed. The recombinant cells could be segregated into three populations based on their cell division and plasmid maintenance abilities: dividing and plasmid-bearing cells, dividing and plasmid-free cells, and viable-but-non-culturable (VBNC) cells. Fed-batch fermentations were performed to investigate the effect of cell segregation on the kinetics of growth and foreign protein production. The results showed that a low concentration of inducer caused weak induction, whereas high levels cause strong induction, resulting in cells segregating into VBNC bacteria and producing a low foreign protein yield. A kinetic model for cell segregation was proposed and its predictions correlated well with experimental data for cell growth and protein expression. The optimal induction strategy could then be predicted by the model, and this prediction was then verified by experimentally deriving the conditions necessary for maximum expression of recombinant protein.

Epidermal Growth Factor↗
PubMed1989

Chemical equivalence of two polyetherpolyurethane foams as a vehicle for povidone-iodine solution: kinetic model for the loss of available iodine.

The loss of available iodine from povidone-iodine solution stored in contact with two different polyetherpolyurethane foams was monitored as a function of time and temperature. Statistical evaluation of the results for the four temperatures studied [ambient (25 degrees), 30, 45 and 55 degrees C] indicated the chemical equivalence of the two foams as storage and delivery systems for povidone-iodine solution in terms of solution stability. In addition, application of a first-order kinetic model to the data produced an acceptable fit. An Arrhenius-type evaluation of the resulting rate constants yielded a linear relationship which was shown to be useful for predicting loss of available iodine under ambient temperature conditions of storage.

Drug Stability↗
PubMed1984

A U-shaped bioartificial pancreas with rapid glucose-insulin kinetics. In vitro evaluation and kinetic modelling.

The lag in insulin release in response to glucose is an obstacle to the development of hybrid pancreatic devices, in which an artificial membrane protects transplanted islets against immune rejection. We designed a U-shaped bioartificial pancreas, in which the blood channel surrounds the islet chamber consisting of two flat membranes; blood circulates successively above the first membrane and then in the reverse direction, below the second membrane. Isolated rat islets were introduced into the chamber, which was perfused with Krebs buffer, and the kinetics of insulin release in response to glucose was determined. During a 20-min, 2.8-20-mM, square-wave glucose stimulation, insulin release in the effluent of the device rose from 0.7 +/- 0.2 to 3.2 +/- 1.0 ng/100 islets/min (P less than 0.05) within 3 min, and reached a maximal level of 12.8 +/- 3.3 ng/100 islets/min at 10 min; 5 min after the return of the glucose concentration to substimulatory level, insulin release dropped from 11.3 +/- 1.5 to 8.0 +/- 1.7 ng/100 islets/min (P less than 0.05), and reached basal value (1.0 +/- 0.2 ng/100 islets/min) 40 min after the end of the stimulation. A 0.1-mM/L/min ramp increase in glucose concentration triggered a significant rise in insulin release (P less than 0.02) when the glucose concentration reached 5.3 +/- 0.2 mM; islets concomitantly perifused within a chamber set up without membrane responded to the same glucose stimulation 5 min earlier. For up to 1000 islets, insulin release in response to glucose was linearly correlated to the number of islets (N = 12, P less than 0.01), indicating that insulin did not significantly inhibit its own secretion in this system. Finally, during glucose stimulation, the insulin concentration in the effluent from the chamber was found to be four times the concentration present at the turning point of the blood channel, suggesting that insulin was transferred into the perfusing medium in part by a countercurrent flux of ultrafiltrate crossing the membranes. We present herein the kinetic modelling of glucose and insulin transfer in this "ultrafiltration chamber," whose functional characteristics are compatible with closed-loop insulin delivery.

Animals↗